title: The degradation of polysorbates 20 and 80 and its potential impact on the stability of biotherapeutics.
abstract: OBJECTIVE
  To study the potential impact of the degradation of Polysorbates (PS) 20 and 80 on the stability of therapeutic proteins in parenteral formulations.
  
  
  METHODS
  First, degradation products of PS20 and 80 were identified. Subsequently, the effect of degraded polysorbate on physical characteristics and long-term stability of protein formulations was assessed. Further, the impact of polysorbate degradation on protein stability was evaluated via shaking stress studies on formulations spiked with artificially degraded polysorbate or degradants like fatty acids. Additionally, aged formulations with reduced polysorbate content were shaken.
  
  
  RESULTS
  The degradation of polysorbate leads to a buildup of various molecules, some of which are poorly soluble, including fatty acids and polyoxyethylene (POE) esters of fatty acids. Spiking studies showed that the insoluble degradants could potentially impact protein stability and that the presence of sufficient intact polysorbate was crucial to prevent this. End-of-shelf-life shaking of protein formulations showed that the stability of various monoclonal antibodies was, however, not affected.
  
  
  CONCLUSIONS
  Although some degradants can potentially influence the stability of the protein (as discerned from spiking studies), degradation of polysorbates did not impact the stability of the different proteins tested in pharmaceutically relevant temperature and storage conditions.
authors.affiliation: Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070 Basel, Switzerland.
authors.forename: Ravuri S K
authors.initials: RS
authors.lastname: Kishore
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kiese
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Astrid
authors.initials: A
authors.lastname: Pappenberger
authors.forename: Ulla
authors.initials: U
authors.lastname: Grauschopf
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011136:Polysorbates / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D011136:Polysorbates; D013501:Surface-Active Agents